Protein carboxyl methyltransferase and methyl acceptor proteins in aging and cataractous tissue of the human eye lens.

We have studied the enzymatic modification of proteins in human eye lens tissue where these molecules can be long-lived and can be exposed to non-enzymatic degradation processes for periods of time up to the age of the individual. We have detected a protein carboxyl methyltransferase that is similar to enzymes from other mammalian tissues which appear to catalyze the methyl esterification of altered aspartyl residues, including D-aspartyl and beta-isomerized L-aspartyl residues, but which have no activity on normal L-aspartyl sites. Upon gel filtration of human lens extracts, we find protein substrates for the lens methyltransferase in each of the major soluble classes of protein. In comparing individual lenses of various ages, protein carboxyl methyltransferase activity was present in tissue from all normal and yellow cataractous lenses tested, but was present only at very low apparent levels in brunescent lens tissue. We find that the methyltransferase is much more highly saturated by endogenous methyl acceptor substrates in lens extracts from older individuals, suggesting that the prolonged in vivo aging of lens protein leads to the accumulation and perhaps metabolism of altered aspartyl residues.